ALK expression in extranodal anaplastic large cell lymphoma favours systemic disease with (primary) nodal involvement and a good prognosis and occursbefore dissemination

Aims-In anaplastic large cell lymphoma (ALCL), the site of origin has been described as an important prognostic factor. Recently, a fusion protein con taining anaplastic lymphoma kinase (ALK) was described in systemic nodal AL CL, and shown to be associated with a good prognosis. The aims of this stud y were to investigate whether the presence of ALK protein differs between A LCL of different sites of origin; to determine whether ALK expression occur s before dissemination to other sites; and, finally, to investigate whether the site of origin remains a prognostic parameter in ALK negative ALCL. Methods-ALK expression, as detected by immunohistochemistry using the monoc lonal antibodies ALK1 and ALKc, was studied in 85 ALCLs from different site s of origin. In 22 patients, ALK expression was studied in multiple biopsie s from different sites (including 13 skin, 16 lymph node, and nine other). Overall survival time was analysed using the Kaplan Meier method. Results-ALK expression was found in 20 of 51 systemic ALCLs with (primary) nodal involvement. No ALK expression was found in 15 primary cutaneous, 14 gastrointestinal, and five nasal ALCLs. Multiple and subsequent biopsies of patients showed ALK expression to be identical to that seen in the primary diagnostic biopsy. Kaplan Meier survival curves showed that in ALK negativ e ALCLs originating from different sites, primary cutaneous cases are assoc iated with an excellent overall survival, whereas the other cases show a co mparable five years survival of less than 40%. Conclusions-If present, ALK expression favours systemic ALCL with (primary) nodal involvement, and can be used in differentiating between extranodal i nvolvement of systemic (nodal) ALCL and primary extranodal ALCL. ALK is exp ressed consistently in multiple biopsies of a given patient, indicating tha t the chromosomal abnormality leading to aberrant ALK expression occurs bef ore dissemination to other sites. Finally, in ALK negative non-cutaneous AL CLs, different sites of origin show comparable poor survival.